A review of research on how flu affects immunosuppressed people and the effects of vaccination on them has been published in The Lancet Infectious Diseases. The authors specifically looked at susceptibility in people with HIV/AIDS, cancer, those who have had a solid organ transplant or bone-marrow transplant and patients on haemodialysis or steroids.

Such groups are thought to be at higher risk of serious influenza-associated complications and as such are priority groups for immunisation.

However, treatments for immune dysfunction may also limit the effectiveness of vaccination and there may be complications from the vaccination itself in these groups. The evidence behind these issues is discussed in this review.

Key points from the review

There is little research on using vaccination to prevent influenza in immunosuppressed people. This review found just one randomised clinical trial. This trial of HIV-infected patients found high vaccine effectiveness.

The same immune dysfunction that can increase the risk and consequences of influenza infection might also compromise vaccine responses and effectiveness.

Most immunosuppressed populations are at higher risk of influenza-associated complications, have a general trend toward impaired antibody responses but can be safely vaccinated.

The priority for control of influenza is focused on generating effective antibody responses with vaccines. Progress is being made at increasing the scale, duration, and breadth of vaccine responses to the two main surface proteins H and N (haemagglutinin and neuraminidase) in both healthy and immuno-compromised populations.

There are two main types of influenza vaccine and both are being developed for the new H1N1 swine flu virus. One involves inactivated vaccines that contain viruses grown in eggs (mostly) and then killed. The other involves live weakened H1N1 vaccines. The researchers say that previous concerns that these live attenuated vaccine would pose a risk to people that are immunocompromised have not been demonstrated by the studies in their review. Research into this area and into and other novel approaches to flu vaccine development are important. They ask that efficacy studies of attenuated vaccines in adults that are immunocompromised are also considered.

Where was the article published?

The research was carried out by Dr Ken M Kunisaki from the Minneapolis VA Medical Center and Edward N Janoff from the University of Colorado Denver School of Medicine.

The study was published in The Lancet Infectious Diseases. It was supported by grants from the National Institutes of Health and the Veterans Affairs Research Service.

What kind of study was this?

In this review, the researchers looked at the susceptibility of immunosuppressed people to the H1N1 swine flu virus, and the possible effectiveness and side effects of upcoming vaccines. Specifically, the authors looked at susceptibility in people with HIV/AIDS, cancer, those who have had a solid organ transplant, or bone-marrow transplant and patients on haemodialysis.

They say: “Although influenza vaccination is widely recommended for people that are immunosuppressed, the same immune dysfunction that can increase the risk and consequences of influenza infection might also compromise vaccine responses and effectiveness.”

The researchers aimed to investigate:

the incidence and mortality rates of influenza infection among adults who are immuno-compromised,

the risks and adverse effects of vaccination,

the ability of a vaccine to get appropriate immune responses, and

the clinical effectiveness of vaccination in these populations.

The researchers searched Medline through the years 1966-2009 for articles on adult influenza, its frequency, complications, and antibody or clinical responses to vaccination. The antibody responses were measured as the percentage of people with levels of antibody protective against H3N2, and the clinical responses were defined as the frequency of influenza reported during the total observation period. They also looked for policy recommendations and guidelines. Excess deaths and hospitalisations were also reported. They only included articles reporting outcomes related to inactivated vaccines, because live attenuated vaccines are not recommended in immuno-compromised groups because there is a theoretical possibility of causing the disease itself.

What was found?

The researchers discussed the following:

HIV/AIDS

Studies show that the numbers of HIV/AIDS patients admitted to hospital with flu has fallen substantially since the introduction of effective antiretroviral therapy. However, admissions are still higher than in the general population.

HIV/AIDS patients generally have lower antibody responses to vaccination, but several studies have shown that vaccination leads to fewer and less severe cases of flu in these patients. Larger randomised trials are needed to assess vaccination, particularly among those with more advanced disease as measured by low CD4+ cell counts.

Transplantation

People who have had solid organ transplants (such as lungs, kidneys or livers) also have higher flu infection rates due to the immunosuppressant drugs they take to prevent organ rejection. Lung transplant recipients are particularly prone to infection and kidney transplant recipients can suffer rejection if they contract flu. In theory, vaccination in these populations could also stimulate a T-cell response, leading to rejection, but the researchers say that most studies say this does not occur.

The intensive pre-transplantation regimens used in preparing people for bone marrow (haematopoetic stem cell) transplants leave patients deeply immunocompromised for up to several months after transplantation. A study on 10 patients’ response to vaccination showed that there was a complete lack of serological response within six months in all 10.

Malignancies and chemotherapy

Chemotherapy can produce major immunosuppression in people with cancer and one study shows that 21-33% of cancer patients contracted flu and were admitted to hospital with respiratory symptoms during one recent seasonal flu epidemic.

Timing of flu vaccination can be crucial in cancer patients. The response might be best between chemotherapy cycles, or more than seven days before chemotherapy starts.

Haemodialysis

Infections are the second leading cause of death in patients on dialysis, and lung infections such as flu are particularly serious. Vaccinated patients on dialysis have been shown to have a lower chance of hospital admission or death from any cause than unvaccinated patients.

Systemic corticosteroids

The authors also looked at people taking oral or inhaled steroids, saying that the evidence shows flu vaccination is both safe and often stimulates an immune response. However, the vaccine’s clinical effectiveness in reducing episodes of flu in people taking the drugs has not been well tested.

What were the researchers’ conclusions?

The researchers say that most immunosuppressed populations are at higher risk of influenza-associated complications. These people have impaired antibody responses to the vaccine (although data for this conclusion is mixed. For example, in some trials, HIV patients with low CD4+ counts developed only 30% of the antibody response of healthy controls, and in one trial of patients on chemotherapy, there was even less of a response. However, other studies have shown that patients who have had haemodialysis and transplant managed up to 80% protective titres.

They say that most immunosuppressed people can be safely vaccinated (although longitudinal data that follows up patients over time are largely lacking).

They also say that the small number of studies of cellular responses to influenza vaccination, in relatively small numbers of immunosuppressed individuals, showed impaired cellular responses among a few patients.

The researchers call for better trial data to inform vaccination recommendations based on the effectiveness and cost in these at-risk populations.

What does the NHS Knowledge Service make of this study?

This study has addressed an important question in vaccination research and one that has become topical with the spread of the new H1N1 swine flu virus. It is disappointing that there are so few high quality trials in this area and that the trials that exist are observational studies. This means that the evidence presented may be prone to bias. Nevertheless, decisions on vaccination in high-risk groups need to be made on the balance of the evidence that exists. This review has presented a useful summary, which can guide practice.